We plan to study the effect of various plasma protein fractions on intratubular pressure, using microperfusion techniques in rats. Preliminary evidence suggests that leakage of protein from the glomerulus leads to partial obstruction or increased resistance to flow of tubular fluid. This in turn reduces GFR. Normal rat proximal tubules will be microperfused with Ringer solution containing various concentrations of rat plasma. Pressure will be monitored down-stream with a second micropipet. If rising pressure is found, further experiments will be carried out in which plasma protein will be separated on a gel filtration column, eluted, and these fractions used in microperfusion experiments in normal rats. The purpose is to identify the class of proteins which may lead to intratubular obstruction. Further studies will be carried out in which rats will be made either acidotic or alkalotic to determine the effect of urine pH on this obstructive process. The possibility that pinocytosis of filtered proteins is responsible for increased resistance to flow (i.e., via cell swelling) will be examined by adding Cytochalasin B to the perfusion fluid. This interferes with pinocytosis, and thus may prevent the effect of intraluminal proteins on flow of tubular fluid.